Triethyl phosphonoacetate → Ethyl 3-(6-(4-(benzyloxy)butoxy)-2-pivalamidopyridin-3-yl)acrylate

HRID 1750072Notes

Reaction equation

HRID 1750072 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.[CH2:17]([O:24][CH2:25][CH2:26][CH2:27][CH2:28][O:29][C:30]1[N:35]=[C:34]([NH:36][C:37](=[O:42])[C:38]([CH3:41])([CH3:40])[CH3:39])[C:33]([CH:43]=O)=[CH:32][CH:31]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C1COCC1>[CH2:17]([O:24][CH2:25][CH2:26][CH2:27][CH2:28][O:29][C:30]1[N:35]=[C:34]([NH:36][C:37](=[O:42])[C:38]([CH3:39])([CH3:40])[CH3:41])[C:33]([CH:43]=[CH:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:32][CH:31]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 21073962N-(6-(4-(benzyloxy)butoxy)-3-formylpyridin-2-yl)pivalamide

Product 1

HCID 66632284Ethyl 3-(6-(4-(benzyloxy)butoxy)-2-pivalamidopyridin-3-yl)acrylateYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under N2, an ice-cooled flask containing THF (100 mL) was charged with sodium hydride (5.7 g, 142.5 mmol) to which ethyl 2-(diethoxyphosphoryl)acetate (32 g, 142 mmol) was added. The ice bath was removed and a solution of intermediate 7 (21.8 g, 56.7 mmol) in THF (120 mL) was slowly added to the preformed anion. The reaction was heated to reflux overnight. The reaction mixture was cooled to rt and partitioned between EtOAc and water. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to give ethyl 3-(6-(4-(benzyloxy)butoxy)-2-pivalamidopyridin-3-yl)acrylate (intermediate 8) (13.3 g, 52%) as a white solid. mp: 75-76° C.

Workup

  1. additionwas added
  2. customThe ice bath was removed
  3. temperatureThe reaction was heated
  4. temperatureto reflux overnight
  5. custompartitioned between EtOAc and water
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with EtOAc
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over anhydrous Na2SO4
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4780da745a764f23bf71e65d59b7f4bc
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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